Drug & supplement interaction

Peppermint + Cyclobenzaprine

Cyclobenzaprine brand names: Cyclobenzaprine, Flexeril, Cycloprine.

Moderate Interaction
The bottom line Moderate

Cyclobenzaprine falls into 2 drug categories that Peppermint can interact with; the most serious is rated moderate. Theoretically, peppermint might increase the levels of CYP3A4 substrates.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Peppermint and Cyclobenzaprine

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Peppermint interacts with whole categories of medication. Cyclobenzaprine falls into 2 of those categories, so it can interact with Peppermint in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

1 of 2

Why this applies to Cyclobenzaprine

Cyclobenzaprine falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Peppermint interacts with.

Theoretically, peppermint might increase the levels of CYP3A4 substrates.
Clinical research in healthy volunteers shows that a single dose of peppermint oil 600 mg inhibits CYP3A4 enzymes and increases the AUC of felodipine, a CYP3A4 substrate. However, in vitro research suggests that peppermint oil only inhibits CYP3A4 at very high concentrations.
Severity Moderate Likelihood Possible Evidence B

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist: your body uses an enzyme called CYP3A4 to help break down cyclobenzaprine. Concentrated peppermint oil (think supplement capsules, not the peppermint in tea or candy) may slow that enzyme down a bit. If it does, more cyclobenzaprine can linger in your system, which could nudge up its usual side effects, things like drowsiness, dizziness, dry mouth, and that foggy, sluggish feeling.

I want to be honest about how shaky this is. The evidence comes from a study using a different drug, and lab work suggests peppermint only blocks this enzyme at very high doses. So for most people the real-world effect is likely small. Still, if you plan to take peppermint oil capsules regularly with cyclobenzaprine, give your pharmacist or doctor a heads-up first.

References
  1. Dresser GK, Wacher V, Wong S, et al. Evaluation of peppermint oil and ascorbyl palmitate as inhibitors of cytochrome P4503A4 activity in vitro and in vivo. Clin Pharmacol Ther 2002;72:247-55. PubMed
  2. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

2 of 2

Cyclobenzaprine also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

Theoretically, peppermint might increase the levels of CYP1A2 substrates.
In vitro and animal research shows that peppermint oil and peppermint leaf inhibit CYP1A2. However, in clinical research, peppermint tea did not significantly affect the metabolism of caffeine, a CYP1A2 substrate. It is possible that the 6-day duration of treatment may have been too short to identify a difference.
Severity Minor Likelihood Possible Evidence B

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist: your body uses an enzyme called CYP1A2 to help break down cyclobenzaprine. In test tube and animal studies, peppermint oil seems to slow that enzyme down a little. If that happened in real life, cyclobenzaprine could hang around longer and feel a bit stronger, meaning more drowsiness, dry mouth, dizziness, or a foggy, sluggish feeling.

The good news is this is mostly theoretical. When peppermint tea was actually tested in people with another CYP1A2 drug, it didn't really change anything. So for most folks this is a minor, low-risk combo. Still, if you notice extra grogginess or you take peppermint oil capsules regularly, mention it to your pharmacist or doctor before changing anything.

References
  1. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
  2. Maliakal PP, Wanwimolruk S. Effect of herbal teas on hepatic drug metabolizing enzymes in rats. J Pharm Pharmacol 2001;53:1323-9. PubMed
  3. Begas E, Tsioutsiouliti A, Kouvaras E, et al. Effects of peppermint tea consumption on the activities of CYP1A2, CYP2A6, Xanthine Oxidase, N-acetyltranferase-2 and UDP-glucuronosyltransferases-1A1/1A6 in healthy volunteers. Food Chem Toxicol 2017;100:80-9 PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Peppermint Also Interacts With Other Medications

Peppermint has 730 moderate, 65 minor known drug interactions in our database — the Cyclobenzaprine one above is among them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Peppermint

Covers the 2,830 medications we’ve checked against Peppermint. Pick one to open its full report.

From our Q&A

Questions About Peppermint or Cyclobenzaprine

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Peppermint or Cyclobenzaprine, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Cyclobenzaprine

This page covers Peppermint only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Cyclobenzaprine page lists 197 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Grapefruit (major), Lithium (major), Procaine (major) and St. John's Wort (major).

By severity: 5 major · 146 moderate · 46 minor.

Open the Cyclobenzaprine interaction page

One more smart check

Taking Peppermint as Part of a Dietary Supplement Product? Check It for Interactions

We hold 1,980 real supplement products containing Peppermint, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Peppermint. Your product may carry other ingredients that interact with Cyclobenzaprine too, on top of Peppermint — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Peppermint and Cyclobenzaprine Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Peppermint
Top 10%

#104 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Cyclobenzaprine
Top 25%

#368 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Peppermint

What is Peppermint?

Peppermint
  • Irritable bowel syndrome (IBS)
  • Indigestion and gas
  • Nausea
  • Tension headache (topical oil)
  • Colds and congestion
  • Freshening breath

Peppermint is a popular herb with the best evidence supporting enteric-coated peppermint oil for easing IBS symptoms. It is generally well tolerated for most adults, but it can cause heartburn and is not recommended in concentrated oil form for infants and young children. Check with your pharmacist or doctor before using it regularly, especially during pregnancy or breastfeeding.

Read the full Peppermint monograph & all interactions
Medication

About Cyclobenzaprine

What Is Cyclobenzaprine Used For?

Brand names: Cyclobenzaprine, Flexeril, Cycloprine

Cyclobenzaprine tablets and extended-release capsules are used alongside rest and physical therapy to relieve muscle spasm caused by acute, painful musculoskeletal conditions — easing pain, tenderness, and limited movement. This use is intended for short-term treatment only (up to 2–3 weeks).

Tonmya, the sublingual (under-the-tongue) form of cyclobenzaprine, is separately indicated for the treatment of fibromyalgia in adults. It is not the same as the oral tablet or capsule formulations.

See full Cyclobenzaprine drug information
Keep checking

Other Drugs & Peppermint

Browse every other medication we’ve checked against Peppermint — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
730Moderate
65Minor
2,034No known interaction
Moderate

730 interactions

Showing 60 of 730 moderate interactions — see all 730 on the Peppermint page.

Minor

65 interactions

Showing 60 of 65 minor interactions — see all 65 on the Peppermint page.

No interaction 2,034 drugs checked — show the list
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
Pharmacist Counseling Corner

Taking Peppermint and Cyclobenzaprine Together: Common Questions

Can you take Peppermint with Cyclobenzaprine?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for Peppermint and Cyclobenzaprine?
Cyclobenzaprine belongs to more than one drug category, and Peppermint interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Peppermint and Cyclobenzaprine interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.